474
Original Investigation
Comparison of health-related quality of life among patients using
novel oral anticoagulants or warfarin for non-valvular atrial fibrillation
Kevser Gülcihan Balcı, Mustafa Mücahit Balcı, Uğur Canpolat, Fatih Şen, Mehmet K. Akboğa,
Muhammed Süleymanoğlu, Serdar Kuyumcu, Orhan Maden, Hatice Selçuk, Mehmet Timur Selçuk
Department of Cardiology, Türkiye Yüksek İhtisas Research and Education Hospital; Ankara-Turkey
ABSTRACT
Objective: The aim of this study was to compare health-related quality of life (HRQoL) measures between novel oral anticoagulants (NOACs)
and warfarin-treated Turkish patients who had been started on oral anticoagulants (OACs) due to non-valvular atrial fibrillation (AF) and to
determine the effects of OACs on patient’s emotional status, anxiety and depression.
Methods: A total of 182 patients older than 18 years with non-valvular AF and being treated with OACs for at least 6 months according to current
AF guidelines who were admitted to outpatient clinics between July 2014 and January 2015 were included in this cross-sectional study. The
exclusion criteria were receiving OACs for conditions other than non-valvular AF and being unable to answer the questionnaire. A questionnaire
was administered to all participants to evaluate HRQoL, depression and anxiety. The mean differences between the groups were compared
using Student’s t-test; the Mann–Whitney U test was applied for comparisons of the medians.
Results: The annual number of hospital admissions was significantly higher in the warfarin group (p<0.001), and all HRQoL scores were significantly lower and Hospital Anxiety and Depression Scale (HADS) score was higher in the warfarin group (p<0.001). History of any type of bleeding was significantly higher in the warfarin group (p<0.001). However, none of the patients had major bleeding. Among patients who experienced
bleeding, all HRQoL scores were significantly lower and HADS score was significantly higher (p<0.001 and p=0.002, respectively).
Conclusion: Warfarin-treated patients had higher levels of self-reported symptoms of depression and anxiety and compromised HRQoL when
compared with NOAC-treated patients. The results may be explained by higher rates of bleeding episodes and higher number of hospital admissions, which may cause restrictions in life while on warfarin treatment. (Anatol J Cardiol 2016; 16: 474-81)
Keywords: atrial fibrillation, warfarin, apixaban, dabigatran, quality of life, anxiety
Introduction
Atrial fibrillation (AF) is the most common arrhythmia in
clinical practice that has been shown to be significantly
associated with increased morbidity and mortality (1). As a
major cardiovascular challenge in the general population, it
should be evaluated by its medical, social and economic
aspects. Medical management of AF patients primarily focuses on the alleviation of AF-related symptoms and prevention
of severe complications associated with AF, such as thromboembolism. In order to prevent AF-related complications,
antithrombotic therapy, control of ventricular rate and treatment of concomitant cardiac diseases should be initiated in
parallel to each other (2). Among the various antithrombotic
and anticoagulant agents, vitamin K antagonists (VKAs) and
novel oral anticoagulants (NOACs) are recommended by most
recent AF guidelines (3, 4).
VKAs have been prescribed for many years for the prevention of thromboembolic events in both valvular and non-valvular
AF (2-4). However, usage of VKAs is complicated due to highly
variable biological effects and their narrow therapeutic index (5,
6). Thus, patients who have been treated with VKAs require
more frequent outpatient visits for monitoring the international
normalised ratio (INR) and also dietary restrictions to lower
vitamin K intake that has a negative impact on health-related
quality of life (HRQoL) among patients (7). Clinical studies have
primarily focused on evaluation of the efficacy and safety of
anticoagulant therapy but not on HRQoL. NOACs have been
developed in recent years that may offer some solution to problems with respect to efficacy, safety and HRQoL (8). They do not
require any periodic blood monitoring for efficacy. Also, they
exhibit a wide therapeutic window and low inter- and intraindividual variability in the dose–effect relation with fewer drug
interactions (8). Therefore, patient’s perception of HRQoL may
differ according to the type of oral anticoagulant (OAC) used.
Address for Correspondence: Dr. Kevser G. Balcı, Park Flora Sitesi B Blok No:4
Yaşamkent Çay yolu, 06810, Ankara-Türkiye
Phone: +90 530 328 38 69 Fax: +90 312 306 10 00 E-mail: kevs84@gmail.com
Accepted Date: 13.05.2015 Available Online Date: 14.07.2015
©Copyright 2016 by Turkish Society of Cardiology - Available online at www.anatoljcardiol.com
DOI:10.5152/AnatolJCardiol.2015.6334
Balcı et al.
Quality of life for non-valvular AF
Anatol J Cardiol 2016; 16: 474-81
197 patients were analysed
for the eligibility of the study
98 patients were on
NOAC therapy
99 patients were on
warfain therapy
7 not included
-2 did not complete all
the questionnaires
-4 were on NOAC therapy less than 6 months
-1 was not treated with
warfain prior to NOAC
therapy
8 not included
-5 did not complete all
the questionnaires
-1 refused to participate
in the study
-2 had no regular followup for INR monitoring
91 included in analysis
91 included in analysis
Figure 1. Flowchart of the study
Therefore, the aim of our study was to compare HRQoL
among Turkish patients in whom oral anticoagulation with VKAs
or NOACs have been initiated for non-valvular AF and also to
assess the impact of OACs on patient’s emotional status, anxiety
and depression.
Methods
In this cross-sectional study, a total of 182 patients (mean
age: 65.5±10.1 years, 49% male) who admitted to our outpatient
clinic peculiar to anticoagulated patients were included between
July 2014 and January 2015 (Fig. 1). A questionnaire was administered to all participants to evaluate their HRQoL. The inclusion
criteria were as follows: age ≥18 years, previous diagnosis of
non-valvular AF, having an indication for OACs according to the
current AF guidelines and being treated with OACs for at least 6
months. Patients receiving OACs for valvular AF, mechanical
heart valve prosthesis or venous thromboembolism and those
who were unable to answer the questionnaire because of cooperation problems were excluded from the study. The study population was categorised into two groups: the ‘warfarin group’ or
the ‘NOAC group’. In the NOAC group, all patients were treated
with warfarin previously and the clinician switched to NOACs at
least 6 months ago because of the labile INRs or complications
with VKAs. The median time from prior warfarin usage in the
NOAC-treated group was 25 (14–52) months. In the NOAC group,
the patients were on dabigatran, apixaban or rivaroxaban treatment, which are approved in Turkey for the prophylaxis of embolism in AF.
The primary outcome of the study was the incidence of
bleeding. A total sample size of 162 patients (81 per group) was
required to detect at least 20% difference with 80% power at 5%
significance level. The difference of 20% was taken from both a
475
pilot study and clinical experience. Sample size estimation was
performed using NCSS and PASS 2000 software (Number
Cruncher Statistical Systems, Kaysville, Utah, USA). Major
bleeding was defined as fatal and symptomatic bleeding and/or
any bleeding requiring blood transfusion and/or 3 g/dL or more
decrease in haemoglobin levels while on OAC treatment (9), as
determined from the electronic medical records or self-report
by the patient. The INR was calculated by raising the prothrombin time ratio (PT of a test sample compared with normal PT) to
the power of a coefficient known as the international sensitivity
index. The intended INR for non-valvular AF was 2.0–3.0. INR
stability was calculated using the INR number within the therapeutic range divided by the collected INR number (for instance,
follow-up INR levels for a patient - INR1=1.4, INR2=1.8, INR3=2.5,
INR4=2.95, INR5=4.7: 2 values within the target level, presented
40% stability). The annual number of hospital admissions was
calculated as follows: (all admissions that were only OAC related since the OAC-therapy first startedx12)/(duration of OAC
therapy in months). Each interview lasted approximately 20 min.
Electronic medical records were also used to obtain sociodemographic and clinical data of participants. All patients gave
informed consent, and the study protocol was approved by the
institutional Ethics Committee.
CHA2DS2-VASc, HAS-BLED and EHRA scores
All patients were evaluated with the original scoring system
to calculate the CHA2DS2-VASc score: congestive heart failure
(1 point); history of hypertension (1 point); age (≥75 years, 2
points; >65 to <75 years, 1 point); diabetes mellitus (1 point);
history of stroke, transient ischemic attack (TIA), peripheral
embolic event (2 points); vascular disease (1 point); female
gender (1 point) (2). Bleeding risk was assessed using the HASBLED score: hypertension (1 point), abnormal renal/liver function
(1 point each), stroke (1 point), bleeding history or predisposition
(1 point), labile INR (1 point), elderly (>65 years, 1 point), drugs/
alcohol concomitantly (1 point each) (2). The European Heart
Rhythm Association (EHRA) score was used to assess the
severity of AF-related symptoms (2): EHRA I: No symptoms; II:
‘Mild symptoms’, normal daily activity not affected; III: ‘Severe
symptoms’, normal daily activity affected and IV: ‘Disabling
symptoms’, normal daily activity discontinued.
Questionnaire
A questionnaire consisting of open-ended questions was
given to the patients during routine outpatient clinic visits.
HRQoL was measured using the self-reported questions of the
Medical Outcomes Study Form 36 (SF-36), which is composed of
8 subscales that reflect both physical health [physical functioning (PF), role-physical (RP), bodily pain (BP) and general health
(GH)] and mental health [vitality (VT), social functioning (SF), role
emotional (RE) and mental functioning (MF)] (10). Scores ranging
from 0 to 100 were obtained, and higher scores indicate better
functioning with fewer problems. The Hospital Anxiety and
476
Balcı et al.
Quality of life for non-valvular AF
Anatol J Cardiol 2016; 16: 474-81
Table 1. Baseline characteristics of the study groups (n=182)
Variables
Warfarin group (n=91)
NOAC group (n=91)
P
Age, years, mean±SD
64.8±10.2
66.2±10.1
Female gender 48 (52.7%)
43 (47.3%)
0.347†
0.459‡
Education level
Uneducated
17 (18.7%)
24 (26.4%)
Primary school
66 (72.5%)
63 (69.2%)
8 (8.8%)
4 (4.4%)
Middle and high school
0.273‡
Marital status
Married
80 (87.9%)
68 (74.7%)
Unmarried (single, divorced or widowed)
11 (12.1%)
23 (25.3%)
Duration of OAC therapy (m)
20 (9–38)
9 (7–12.5)
Medication Warfarin
91 (100%)
-
Dabigatran 150 mg bid
-
37 (40.7%)
Dabigatran 110 mg bid
-
10 (11.0%)
Rivaroxaban 20 mg od
-
16 (17.6%)
Apixaban 5 mg bid
-
26 (28.6%)
Apixaban 2.5 mg bid
-
2 (2.2%)
LVEF, %
55 (15–65)
60 (15–60)
Hypertension, n (%)
67 (73.6%)
66 (72.5%)
Coronary artery disease, n (%)
54 (59.3%)
38 (41.8%)
Diabetes mellitus, n (%)
17 (18.7%)
18 (19.8%)
Heart failure, n (%)
27 (29.7%)
25 (27.5%)
3 (1–8)
3 (1–7)
70 (76.9%)
78 (85.7%)
12.8±3.5
5.0±1.3
CHA2DS2–VASc, median
MC (MMAS-4 scores of <2, n (%)
AN of hospital admissions, mean±S.D.
0.022‡
<0.001¶
-
0.267¶
0.867‡
0.018‡
0.851‡
0.743‡
0.421¶
0.128‡
<0.001†
EHRA score, median, min–max
1
34 (37.4%)
54 (59.3%)
2
44 (48.4%)
26 (28.6%)
3
13 (14.3%)
10 (11.0%)
4
0 (0.0%)
1 (1.1%)
0.010¶
HAS-BLED score
0–2
72 (79.1%)
68 (74.7%)
≥3
19 (20.9%)
23 (25.3%)
0.824¶
†Student’s t-test, ‡Pearson chi-square test, ¶Mann–Whitney U test; AN: annual number, CHA2DS2-VASc: congestive heart failure, history of hypertension, age, diabetes mellitus,
history of stroke/TIA/embolic event, vascular disease, female gender; EHRA - European Heart Rhythm Association; HAS-BLED - hypertension, abnormal renal/liver function, stroke,
bleeding history or predisposition, labile international normalised ratio, elderly, drug/alcohol use; LVEF - left ventricular ejection fraction; m: months; MC - medical compliance; MMAS
- Morisky Medication Adherence Scale; NOAC - novel oral anticoagulant
Depression Scale (HADS) was used to determine the depression
and anxiety scores of the patients (11). The HADS consists of 14
items that include a 7-item depression scale (HADS-D) and a
7-item anxiety scale (HADS-A). Anxiety scores were evaluated
over 21 points; scores ranging from 8 to 10 points were considered
as having tendency for anxiety, whereas scores of 10 or more
points were considered as having anxiety (12). As for depression,
scores were evaluated over 21 points; 5–7 points were consid-
ered as having tendency for depression, whereas scores greater
than 7 points were considered as having depression (12). The
Morisky Medication Adherence Scale (MMAS) was used to
determine medical compliance (13); patients with MMAS-4 scores
of <2 were considered as highly adherent and compliant with OAC
treatment in our study. Uneducated patients answered the questionnaire with the help of an educated relative or a doctor without
any manipulation.
Balcı et al.
Quality of life for non-valvular AF
Anatol J Cardiol 2016; 16: 474-81
120
Warfarin
P<0.001
NOAC
477
P<0.001
100
Score
80
60
40
20
0
PF
RP
BP
GH
VT
SF
RE
MH
Figure 2. Comparison of health-related quality of life measures
between the study groups
BP - bodily pain; GH - general health; MF - mental functioning; NOAC - novel oral
anticoagulant; PF - physical functioning; RE - role emotional; RP - role-physical; SF - social
functioning; VT - vitality
10
Warfarin
NOAC
P<0.001
Score
8
6
NOAC - novel oral anticoagulant
for age, gender, time interval for anticoagulation and medical
compliance. Multiple logistic regression analysis was applied for
determining the difference between the warfarin and NOAC
groups for bleeding after adjustment for all possible confounding factors (i.e. age, gender, anticoagulation time and medical
compliance). Odds ratios and 95% confidence intervals for each
independent variable were also calculated. A two-sided p value
of <0.05 was considered statistically significant.
Results
4
2
0
Figure 4. Comparison of the percentage of patients who experienced a
bleeding episode between the study groups
HADS-A
HADS-D
Figure 3. Comparison of Hospital Anxiety and Depression Scale scores
between the study groups
HADS - Hospital Anxiety and Depression Scale; HADS-A - anxiety subscale of HADS;
HADS-D - depression subscale of HADS; NOAC - novel oral anticoagulant
Statistical analysis
Data analysis was performed using SPSS for Windows, version 11.5 (SPSS Inc., Chicago, IL, US). Data were shown as
mean±SD or median (min–max), where applicable. The mean
differences between the groups were compared using Student’s
t-test; the Mann–Whitney U test was applied for comparisons of
medians. Nominal data were analysed by Pearson’s chi-square
test. Degrees of association between continuous variables were
evaluated using Spearman’s rank correlation analyses.
Whether the differences in HRQoL, HADS-A and HADS-D
scores and annual number of hospital admissions between the
warfarin and NOAC groups were to be continued or not were
evaluated by analysis of covariance (ANCOVA) after adjustment
The baseline characteristics of the study population are
shown in Table 1. The socio-demographic and clinical parameters were similar between the study groups except for marital
status and history of coronary artery disease (p=0.022 and
p=0.018; respectively). CHA2DS2-VASc and HAS-BLED scores
did not differ between the study groups (p=0.421 and p=0.824,
respectively). The duration of OAC therapy was significantly
longer in the warfarin group than in the NOAC group (p<0.001),
and the annual number of hospital admissions was significantly
higher in the warfarin group (p<0.001). Among warfarin-treated
patients, only 24 (27%) showed INR stability up to 50% and 10
(11%) presented stability of 75% or above. Of these patients, 34
(37.3%) patients had effective INR levels.
All HRQoL scores (PF, RP, BP GH, VT, SF, RE and MF) were
significantly lower and HADS-A/HADS-D scores were higher in
the warfarin group (p<0.001) (Fig. 2, 3). Correlation analysis
revealed that there was a significant negative correlation
between EHRA scores and HRQoL scores (PF, r=–0.624; RP,
r=–0.507; BP, r=–0.532; GH, r=–0.558; VT, r=–0.451; SF, r=–0.481;
RE, r=–0.376 and MF, r=–0.375; p<0.001), but no relationship was
observed between EHRA and HADS scores (p>0.05). The annual
number of hospital admissions showed a negative correlation
with all HRQoL scores and a positive correlation with HADS-A
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Balcı et al.
Quality of life for non-valvular AF
Anatol J Cardiol 2016; 16: 474-81
Table 2. Correlation analysis showing the association of quality of life,
anxiety and depression levels with EHRA score and annual number of
hospital admissions
EHRA score
Annual number
hospital admissions
R
P†
R
P†
Physical functioning 0.624 <0.0010.375<0.001
Role physical
0.507 <0.0010.410<0.001
Bodily pain
0.532 <0.0010.328<0.001
General health
0.558 <0.0010.371<0.001
Vitality
0.451 <0.0010.402<0.001
Social functioning
0.481 <0.0010.600<0.001
Role emotional
0.376 <0.0010.493<0.001
Mental functioning 0.375 <0,0010.269<0.001
HADS-A
0.073 0.326 0.397<0.001
HADS-D
0.018 0.813 0.260<0.001
†Spearman’s correlation analysis; EHRA - European Heart Rhythm Association; HADS
- Hospital Anxiety and Depression Scale; HADS-A - Anxiety subscale of HADS;
HADS-D - Depression subscale of HADS
Table 3. Comparison of unfavourable effects of oral anticoagulant
therapies (n=182)
Variables
History of bleeding, n (%)
Warfarin group NOAC group
(n=91)(n=91)
P
40 (44.0%)
5 (5.5%)
Type of bleeding, n (%)
Gingival bleeding
10 (11.0%)
1 (1.1%)
Bruising
13 (14.3%)
1 (1.1%)
Melena
2 (2.2%)
-
Haematuria
4 (4.4%)
-
11 (12.1%)
3 (3.3%)
Epistaxis
<0.001‡
-
‡Pearson chi-square test, NOAC - Novel oral anticoagulant
and HADS-D scores (PF, r=–0.375; RP, r=–0.410; BP, r=–0.328;
GH, r=–0.371; VT, r=–0.402; SF, r=–0.600; RE, r=–0.493; MF,
r=–0.269; HADS-A, r=0.397 and HADS-D, r=0.260; p<0.001)
(Table 2). History of any type bleeding after starting OAC therapy was significantly higher in the warfarin group than in the
NOAC group (p<0.001) (Fig. 4). However, none of patients had
major bleeding (Table 3). In the warfarin-treated group, all
bleeding episodes occurred when INR levels were ≥2.5. At the
time of the bleeding episode, there was no concomitant trauma
and/or intervention and median INR was 3.7 (2.5–6.0). Among
patients who experienced bleeding, all HRQoL scores were
significantly lower and the HADS-D score was significantly
higher (p<0.001 and p=0.002, respectively) (Table 4). When
patients were analysed according to having effective INR levels, none of the HRQoL scores showed any significant difference between the groups (p>0.05); however, higher HADS-A
and HADS-D scores were observed in the ineffective INR level
Table 4. Comparison of quality of life, anxiety and depression levels of
patients according to the occurrence of any type bleeding event
(n=182)
Variables
Bleeding (-) Bleeding (+)
(n=137)(n=45)P†
Physical functioning
71.3±21.2
53.1±20.5
<0.001
Role physical
70.8±28.0
38.3±31.3
<0.001
Bodily pain
75.5±23.3
52.2±27.6
<0.001
General health
55.9±20.6
34.2±22.8
<0.001
Vitality
55.4±19.8 39.6±19.9<0.001
Social functioning
76.2±21.3
49.2±23.4
<0.001
Role emotional
69.3±25.6
45.9±23.9
<0.001
Mental functioning
68.6±14.5
59.6±14.1
<0.001
HADS-A
5.3±1.4 5.5±1.50.352
HADS-D
4.2±1.3 4.8±1.30.002
†Student’s t-test, HADS - Hospital Anxiety and Depression Scale; HADS-A - Anxiety
subscale of HADS; HADS-D - Depression subscale of HADS
group [HADS-A: 5 (3–8) vs. 4 (3–7), p=0.003; HADS-D: 4 (2–6) vs.
3 (2–6), p=0.013].
After covariance adjustment for age, gender, duration of
OAC therapy and drug compliance, all HRQoL scores were still
significantly lower in the warfarin group (p<0.05), and HADS
scores and the annual number of hospital admissions were
significantly higher in the warfarin group (p<0.001) (Table 5). In
multivariate logistic regression analysis, after adjustment
according to the age, gender, duration of OAC therapy and drug
compliance, usage of warfarin (OR: 31.1; 95% CI: 5.82–166.3,
p<0.001) and older age (OR: 1.067; 95% CI: 1.011–1.126, p=0.018)
were found as independent predictors for occurrence of
bleeding events.
Discussion
Our study results showed that all HRQoL scores were significantly lower and HADS scores were significantly higher in
the warfarin group than in the NOAC group. The annual number
of hospital admissions was significantly higher in the warfarin
group, which showed a negative correlation with all subscales
of HRQoL questionnaire and a positive correlation with HADS-A/
HADS-D scores. Warfarin-treated patients experienced more
bleeding episodes, and all HRQoL scores were significantly
lower and the HADS-D score was significantly higher among
patients who had a bleeding episode. Also, warfarin treatment
and older age conferred greater risks for bleeding.
HRQoL objects to get information about difficulties of living
with a disease that are variable for each patient due to the
subjective and diverse perception (14). Improvement in functional capacity or alleviation of AF-related symptoms (7) is not
aimed at when using OACs in AF patients; OACs protect
patients from thromboembolic complications. Chronic use of
VKAs constitutes a well-defined risk without any symptomatic
Balcı et al.
Quality of life for non-valvular AF
Anatol J Cardiol 2016; 16: 474-81
479
Table 5. Comparison of quality of life, anxiety, depression levels and annual number of hospital admissions between warfarin and NOAC groups
after adjusting for age, gender, duration of OAC therapy and drug compliance
Warfarin group (n=91)
NOAC group (n=91)
P†
Physical functioning
58.8 (52.5–65.0)
68.4 (60.9–75.8)
0.100
Role physical
45.6 (36.3–54.9)
73.8 (62.8–84.8)
<0.001
Bodily pain
57.2 (49.4–65.0)
77.1 (67.9–86.4)
0.006
General health
40.0 (33.5–46.5)
55.4 (47.7–63.1)
0.011
Vitality
44.1 (38.1–50.2)
57.4 (50.2–64.6)
0.019
Social functioning
53.9 (48.0–59.9)
82.2 (75.2–89.2)
<0.001
Role emotional
45.7 (38.1–53.3)
78.0 (69.0–87.0)
<0.001
Mental functioning
60.3 (55.7–64.9)
70.4 (65.0–75.9)
0.019
6.2 (5.8–6.6)
4.6 (4.2–5.1)
<0.001
4.9 (4.5–5.3)
3.6 (3.1–4.1)
<0.001
12.8 (11.9–13.7)
4.9 (3.8–6.0)
<0.001
Variables
HADS-A
HADS-D
Annual number of hospital admissions
†Analysis of covariance (ANCOVA); data were given as mean (95% confidence interval) after adjusting for age, gender, duration of oral anticoagulant therapy and drug compliance;
HADS - Hospital Anxiety and Depression Scale; HADS-A - Anxiety subscale of HADS; HADS-D - Depression subscale of HADS
benefit that results in lifestyle changes and influences HRQoL
(15). Before the development of NOACs, VKAs were widely used
for the prophylaxis of thromboembolic events; however, requirement for strict blood monitoring has a negative impact on HRQoL
in such patients (14). Therapy with VKAs is complicated because
of their variable biological effects, necessity for dietary restrictions, narrow therapeutic index and adverse events such as
thrombotic and bleeding events (5, 14).
Several studies have investigated the effect of OAC therapy
on HRQoL (16). Corbi et al. (15) found worse scores of HRQoL
among women, elderly, those with less than 1 year of therapy
and those with an indication other than metallic prosthetic heart
valve for OAC use. In their study group, warfarin was the most
prescribed OAC (83.1%). They suggested that patients with longer use of OAC (>10 years) had enough time to adapt to the
therapy. In our study, the median duration of OAC therapy was 20
months in the warfarin group and 9 months in the NOAC group.
When compared with the previous study, the anticoagulation
time was relatively shorter in our study cohort. Although we
observed a longer duration of therapy in the warfarin group
when compared with the NOAC group, we observed worse
HRQoL scores among warfarin users. Somehow NOAC-treated
patients mostly had better EHRA scores that may lead to better
HRQoL scores. We thought that due to the limited clinical experience with NOACs, clinicians might prefer to use NOACs among
relatively more healthy subjects because they may experience
lesser side effects or when they face them, they may recover
easily. Lancaster et al. (17) observed no significant difference
between warfarin-treated and control patients regarding HRQoL
until a bleeding episode had occurred. They concluded that patients
with bleeding episode had a significant decrease in perceived
health. We observed higher minor bleeding events in the warfarin
group and worse HRQoL scores were noted in the warfarin group.
Although in the warfarin group, the duration of therapy was longer
than that in the NOAC group, after adjustment according to the
duration of OAC therapy, usage of warfarin was still an independent
predictor of bleeding events. In a study conducted by Alegret et al.
(18), they observed worse HRQoL related to some aspects among
VKA-treated patients as compared with NOAC-treated patients.
However, the difference between the two groups disappeared after
6 months of therapy. Moreover, Monz et al. (19) failed to show any
difference in HRQoL measures between warfarin and dabigatrantreated patients despite the known complexities of warfarin treatment. In the Turkish population, less than half of the patients (41.3%)
who were on OAC treatment had effective INR levels and 11% of
them had labile INR value (1), which may directly worsen warfarintreated patients’ HRQoL. Therefore, we observed that warfarintreated patients had worse HRQoL scores than NOAC-treated
patients beyond the 6 months of therapy (20 vs. 9 months).
HADS is a reliable and valid instrument to assess depression
and anxiety in patients and in the general population (20). We
observed a positive correlation between HADS scores and the
annual number of hospital admissions, which means that the
warfarin group was more prone to anxiety and depression. In
our study, 37.3% patients had INR levels between 2.0 and 3.0,
which is consistent with the results of the AFTER study (41.3%)
(1). When we analysed patients according to having effective
INR levels, higher HADS scores were observed among patients
with ineffective INR levels. We think that difficulties of gaining
an effective INR level may have an important influence on
patients’ emotional status. In a previous study, treatment with
NOACs revealed better HADS scores among elderly AF patients
and treatment with NOACs was psychologically well accepted
than warfarin therapy (21). We can conclude that NOACs may
have positive effects on anxiety and depression symptoms in
non-valvular AF patients.
Social desirability, described as the tendency to answer questions in a socially accepted manner for preserving self-image or
480
Balcı et al.
Quality of life for non-valvular AF
avoiding negative consequences (22), may be another reason for
better HRQoL assessment and better HADS scores in the NOAC
group. All patients in the NOAC group had previously switched from
warfarin to NOAC therapy due to labile INRs or complications; this
may have led them to report better results with the new medication
to represent a favourable image. In addition to the lack of frequent
laboratory follow-up with NOACs, being treated with a more expensive drug may improve patients’ perception of HRQoL (23).
Study limitations
This study has several limitations. First, this was a crosssectional study with a relatively small sample size. Second, it
was a single-centre study. Third, in the NOAC group, we did not
classify the patients according to the type of NOACs; instead, all
patients were evaluated together. Fourth, in the NOAC group, we
included only those patients who had previously used warfarin,
which may have given them an opportunity to compare both OAC
therapies; on the other hand, it may have led to a bias. Finally, the
questionnaire for assessing HRQoL was not particular to our
study population, but it evaluates patients’ perception of their
health status and both physical and functional dimensions in
addition to emotional and social ones. In this context, modified
questionnaires for the Turkish population may provide precise
evaluation of the current issue.
Conclusion
Warfarin-treated patients had higher levels of self-reported
symptoms of depression and anxiety and compromised HRQoL
when compared with NOAC-treated patients. The results may be
explained by the higher rates of bleeding episodes and higher
number of hospital admissions, which may cause restrictions in
life while on warfarin treatment.
Conflict of interest: None declared.
Anatol J Cardiol 2016; 16: 474-81
3.
4.
5.
6.
7.
8. 9. 10.
11.
12.
13.
Peer-review: Externally peer-reviewed.
Author contributions: Concept - K.G.B., M.M.B.; Design - K.G.B.,
M.M.B., O.M., M.T.S., H.S., U. C.; Supervision - O.M., M.T.S., H.S.;
Resource - M.S., S.K., K.G.B., M.K.A.; Data collection &/or processing U.C., F.Ş., K.G.B., M.K.A., M.S., S.K.; Analysis &/or interpretation M.M.B., M.S., S.K., O.M., F.Ş., K.G.B., M.K.A.; Literature search - M.M.B.,
O.M., F.Ş., K.G.B., M.K.A., U.C., M.S., S.K.; Writing - K.G.B., M.M.B., O.M.,
M.T.S., H.S.; Critical review - O.M., M.T.S., H.S., U.C.
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